Polymer supported catalysts are widely used in chemical processes. Much of the technology that is presently available derives from the solid-phase peptide synthesis techniques developed by Merrifield. These techniques are based on insoluble cross-linked polystyrene supports. Catalysts supported on Merrifield resins can be recovered from reaction media using a solid/liquid separation technique such as filtration.
With the growing interest in environmentally friendly, or “green” chemical processes, there is an emphasis on the ability to reuse materials and to minimize amounts of solvents required for a given process. Filtration is typically a relative solvent-intensive process, because the recovered solid is typically rinsed with additional solvent. Further, some polymer supported catalysts suffer from decreased activity once they are isolated via filtration. This impacts their potential to be reused multiple times.
Soluble polymer supported catalysts have been developed. These catalysts can be recovered from the reaction medium either by precipitation followed by filtration, by liquid/liquid separation, or by ultrafiltration using a filtration membrane. Precipitation/filtration obviously suffers from the same drawbacks associated with the filtration of insoluble polymer supported catalysts, described above. Inadequate partitioning of the catalyst into the desired liquid phase often impairs liquid/liquid separations. For example, liquid/liquid separation is impractical if the catalyst and the product are both soluble in the same phase. Ultrafiltration of soluble catalysts using membranes has enjoyed some success, but the recycled catalysts often suffer from some loss of activity.
An alternative way of using a soluble catalyst is to use a biphasic system wherein the catalyst is preferentially soluble in one phase and the substrate and/or products are soluble in the other phase. During reaction, the biphasic solvent system is vigorously mixed to ensure maximum contact between the catalyst and substrate. After reaction, the mixture is allowed to settle and the product phase is removed, leaving the catalyst phase available for recycling. The drawback to biphasic systems is that the presence of multiple phases introduces kinetic barriers to reaction.
The drawbacks associated with biphasic solvent systems can be overcome by using a solvent system that is monophasic under one set of conditions and biphasic under a different set of conditions. For example, liquid-liquid biphasic systems that exhibit an increase in phase miscibility at elevated temperature together with soluble polymer-bound catalysts that have a strong phase preference at ambient temperature are described in “Palladium-Catalyzed C—C Coupling under Thermomorphic Conditions,” by Bergbreiter, et al., J. Am. Chem. Soc., 2000, 122, 9058–64 and in “Nonpolar Polymers for Metal Sequestration and Ligand and Catalyst Recovery in Thermomorphic Systems,” by Bergbreiter, et al., J. Am. Chem. Soc., 2001, 123, 11105–06.
There is a need in the art for catalytic methods that allow for the efficient separation of the catalyst from the reaction product and the recycling of the catalyst. It is desirable that such methods operate with minimal additional solvent to effect the separation of the catalyst.